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Published 15 March 2004. doi:10.1083/jcb.200309112
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 164, Number 6, 935-941
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Article

 Tumor cell {alpha}3ß1 integrin and vascular laminin-5 mediate pulmonary arrest and metastasis

Hui Wang1, Weili Fu1, Jae Hong Im1, Zengyi Zhou1, Samuel A. Santoro3, Vandana Iyer5, C. Mike DiPersio5, Qian-Chun Yu2, Vito Quaranta4, Abu Al-Mehdi6, and Ruth J. Muschel1

1 Department of Pathology, Children's Hospital of Philadelphia, Philadelphia, PA 19104
2 Department of Pathology, University of Pennsylvania, Philadelphia, PA 19104
3 Department of Pathology, Vanderbilt University, Nashville, TN 37322
4 Department of Cancer Biology, Vanderbilt University, Nashville, TN 37322
5 Department of Cell Biology, Albany Medical College, Albany, NY 12208
6 Department of Pharmacology, University of South Alabama, Mobile, AL 36688

Address correspondence to Ruth J. Muschel, Dept. of Pathology, Rm. 916D ARC, Children's Hospital of Philadelphia, 3615 Civic Center Blvd., Philadelphia, PA 19104. Tel.: (267) 426-5481. Fax: (267) 426-5483. email: muschel{at}xrt.upenn.edu

Arrest of circulating tumor cells in distant organs is required for hematogenous metastasis, but the tumor cell surface molecules responsible have not been identified. Here, we show that the tumor cell {alpha}3ß1 integrin makes an important contribution to arrest in the lung and to early colony formation. These analyses indicated that pulmonary arrest does not occur merely due to size restriction, and raised the question of how the tumor cell {alpha}3ß1 integrin contacts its best-defined ligand, laminin (LN)-5, a basement membrane (BM) component. Further analyses revealed that LN-5 is available to the tumor cell in preexisting patches of exposed BM in the pulmonary vasculature. The early arrest of tumor cells in the pulmonary vasculature through interaction of {alpha}3ß1 integrin with LN-5 in exposed BM provides both a molecular and a structural basis for cell arrest during pulmonary metastasis.

Key Words: metastasis; tumor cell; integrin; laminin; vessel

Abbreviations used in this paper: BM, basement membrane; LN, laminin.


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